Yan Leyfman, Medical Oncologist, Co-Founder and Executive Director of MedNews Week, shared a post by Jeremy Bellaiche, Founder of Shuf, on LinkedIn, adding:
“Can we finally make CAR-T work for T-cell leukemias?
In this week’s episode of The Translational Edge, we explore one of the most exciting advances in cellular therapy: the first universal base-edited CAR-T cells for T-ALL.
T-cell acute lymphoblastic leukemia has long been one of the most difficult diseases for CAR-T therapy. Unlike B-ALL, malignant T cells share many of the same targets as therapeutic T cells – creating major barriers like fratricide and graft-versus-host disease.
Researchers tackled this with precise base editing, performing three simultaneous genetic edits:
- TCRαβ knockout – prevents GVHD.
- CD52 knockout – enables alemtuzumab lymphodepletion without destroying the CAR-T cells.
- CD7 knockout – prevents fratricide while allowing CD7 targeting on leukemia cells.
The early results are remarkable:
- 11/11 patients achieved complete morphologic remission by day 28.
- 82% reached deep MRD negativity.
This represents a major step toward universal, immune-stealth, off-the-shelf CAR-T therapies.
Challenges remain – viral reactivations, antigen escape, and toxicity optimization – but the trajectory of the field is unmistakable.
If you’re interested in the future of gene editing, cellular therapy, and translational oncology, this episode is for you.
Listen to Episode 15.”
Quoting Jeremy Bellaiche‘s post:
“Excited to share the episode 15 of The Translational Edge with Yan Leyfman, MD exclusively on Shuf ! The First Universal Base-Edited CAR T Cells for T-ALL.
- T-cell acute lymphoblastic leukemia (T-ALL) behaves differently than B-ALL: It relapses aggressively.
- Base editing was used to perform three simultaneous C to T edits that turned off (TCRαβ to prevents GVHD, CD52 to allow patients to receive alemtuzumab lymphodepletion without killing the CAR-T product, CD7 to prevent fratricide and enable targeting of CD7 on leukemia cells).
- All 11 patients achieved complete morphologic remission by day 28, with 82% reaching deep MRD negativity (flow or PCR <10⁻⁴)
- The field is clearly moving toward universal, immune-stealth, multi-edited, off-the-shelf cellular therapies.
- We still have hurdles: viral reactivations, CD7-negative escape, toxicity optimization. But the direction is unmistakable.
Link to episode.”
Other articles about CAR-T Therapy on OncoDaily.